the ISMP Canada databases, and 44 were found in the THEME: Knowledge Gaps Subtheme: Wrong dose Because each device is designed to supply only a name. This situation can result when a prescription Incident Example Acknowledgements References Institute for Safe Medication Practices Canada A KEY PARTNER IN NSIR database. Incidents not related to epinephrine single, measured dose when activated, choosing the prepared for a specific patient is returned to stock in A physician wrote a prescription for “Twinrix” with 1. Wood RA, Camargo CA Jr, Lieberman P, Sampson HA, Schwartz LB, Zitt M, et al. Anaphylaxis in America: the prevalence and REPORT MEDICATION INCIDENTS Online: www.ismp-canada.org/err_index.htm use in anaphylaxis were excluded, which left 146 Subtheme: Wrong route Incorrect dose incidents with epinephrine have correct one is essential. the pharmacy, because the patient either does not pick 6 refills. The pharmacist clarified with both the ISMP Canada gratefully acknowledges the characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467. Phone: 1-866-544-7672 incidents in the final analysis. The analysis was occurred in both acute care and community settings. up the prescription or declines to purchase it because patient and the physician that the desired contribution of content by Waleed Alqurashi MD, 2. Tejedor-Alonso MA, Moro Moro M, Múgica-García M. Epidemiology of anaphylaxis: contributions from the last 10 years. J Investig Allergol Clin Immunol. 2015;25(3):163-175. conducted according to the methodology for For anaphylaxis, epinephrine should be administered One potential contributing factor has been use of the of cost. These types of incidents highlight problems medication was Twinject. MSc, FAAP, FRCPC, Assistant Professor, University 3. Anaphylaxis and allergy in the emergency department.Ottawa (ON): Canadian Institute for Health Information; 2015 Sep 10 [cited multi-incident analysis outlined in the Canadian intramuscularly (IM); the intravenous (IV) route of historical ratio expressions (1:1000, 1:10,000) for in 2 community pharmacy processes—the process to of Ottawa Department of Pediatrics and Emergency 2017 Mar 20]. Available from: https://secure.cihi.ca/free_products/Anaphylaxis_Infosheet_en.pdf Incident Analysis Framework.4 administration should be reserved for patients who strength. In 2016, because of an ongoing stream of return a product to stock, and the dispensing process LASA issues were also reported from the hospital Medicine Children’s Hospital of Eastern Ontario 4. Incident Analysis Collaborating Parties. Canadian incident analysis framework. Edmonton (AB): Canadian Patient Safety Institute; have not responded to IM doses and those serious errors related to confusion in understanding for labelling and verification of both the outer setting, where ePHEDrine was mistaken for (CHEO), ON and Ken J Farion MD FRCPC, Medical 2012 [cited 2016 Nov 14]. Incident Analysis Collaborating Parties are Canadian Patient Safety Institute (CPSI), Institute for Safe Quantitative Findings experiencing severe physiologic compromise.5 ratio expressions, the United States Pharmacopoeia packaging and the device inside the box. epinephrine when medication vials were being Director – Quality & Systems Improvement, Medication Practices Canada, Saskatchewan Health, Patients for Patient Safety Canada (a patient-led program of CPSI), Paula Beard, Volume 17 • Issue 6 • June 29, 2017 Carolyn E. Hoffman, and Micheline Ste-Marie. Available from: http://www.patientsafetyinstitute.ca/en/toolsResources/Incident Wrong-route administration of epinephrine has been eliminated ratio expressions on single-entity drug re-stocked. Children’s Hospital of Eastern Ontario, Ottawa, ON Analysis/Documents/Canadian%20Incident%20Analysis%20Framework.PDF The majority of the incidents were reported to the previously reported in an ISMP Canada Safety products such as epinephrine.10 Therefore, 1:1000 Incident Example and acknowledges the following individuals for their 5. Lieberman P, Nicklas RA, Randolph C, Oppenheimer J, Bernstein D, Ellis A et al. Anaphylaxis—a practice parameter update 2015. ISMP Canada databases. Of these reports, wrong Bulletin6 and elsewhere in the literature.7,8 In a review epinephrine products are now labelled as 1 mg/mL, An Epi-Pen was dispensed for a child. The expert review of this bulletin: Ann Allergy Asthma Immunol. 2015;115(5):341-384. Epinephrine Use for Anaphylaxis – A Multi-Incident Analysis dose errors (e.g., Epipen Jr. given to a child weighing of more than 600 cases reported to the Pennsylvania while epinephrine 1:10,000 for IV injection is caregiver at school noticed that the device was 6. Alert: wrong route incidents with epinephrine. ISMP Canada Saf Bull 2014 [cited 2017 Feb 2];14(4):1-3. Available from: https://www.ismp-canada.org/download/safetyBulletins/2014/ISMPCSB2014-4_Epinephrine.pdf 30 kg or greater) comprised the most commonly Patient Safety Reporting System, wrong-route errors labelled as 0.1 mg/mL. A second potential factor labelled with someone else’s name, even though the Waleed Alqurashi MD, MSc, FAAP, FRCPC, 7. Campbell RL, Bellolio MF, Knutson BD, Bellamkonda VR, Fedko MG, Nestler DM, et al. Epinephrine in anaphylaxis: higher risk of reported incident type, followed by products being involving IV administration were responsible for contributing to incorrect dosing is the need for a dose Pediatric devices contain an epinephrine dose outer box was labelled correctly. The school Assistant Professor, University of Ottawa Department cardiovascular complications and overdose after administration of intravenous bolus epinephrine compared with intramuscular of anaphylaxis is increasing.2,3 The Canadian Institute prepared for the wrong patient and wrong quantity 25.4% of all epinephrine adverse events and 63.3% of calculation in the pediatric age group. The appropriate for a child weighing between 15 to 30 kg notified the parents, who contacted the pharmacy. of Pediatrics and Emergency Medicine Children’s epinephrine. J Allergy Clin Immunol Pract. 2015;3(1):76-80. Hospitals: for Health Information (CIHI) reported that from dispensed. Over 80% of incidents were caught before the harmful events.8 Several studies have attributed epinephrine dose for anaphylaxis in pediatrics must (i.e., 0.15 mg); the ‘adult’ device delivers 0.3 mg and The pharmacy determined that the device provided Hospital of Eastern Ontario (CHEO), ON; Stephanie 8. An update on the “Epi”demic: events involving EPINEPHrine. Pa Patient Saf Advis. 2009;6(3):102-103. 9. Cohen MB, Saunders SS, Wise SK, Nassif S, Platt MP. Pitfalls in the use of epinephrine for anaphylaxis: patient and provider • Consider the use of epinephrine auto-injectors 2006 to 2015, there was a 64% increase in the the error reached the patient. this error to a lack of adequate education of be calculated according to the patient’s weight is recommended for children (and adults) weighing for the child had previously been returned to stock Crampton, RN, BSN, ENC(C), Cornwall Hospital, 9 11 12 opportunities for improvement. Int Forum Allergy Rhinol. 2017;7(3):276-286. or prepared anaphylaxis kits with appropriate number of individuals for whom an epinephrine healthcare professionals. (0.01 mg/kg, up to a maximum of 0.5 mg); this 30 kg or more. In several of the incidents analyzed, without removal of the old label. Cornwall, ON; Tracy Furst, BSc, BScPharm, 10. Changes in expression of strength: elimination of ratios on single-entity injectable products. ISMP Can Saf Bull 2016 [cited 2017 labelling to support correct epinephrine dose auto-injector was dispensed, and children were the Of the incidents reported to ISMP Canada databases, calculation step represents a risk for error. verification of the child’s weight at the pharmacy Children's Emergency Department Pharmacist, Feb 12]; 16(2):1-3. Available from: and route of administration. top consumers.3 Because of the increased use of 3.5% of cases resulted in harm to the patient. The Incident Example allowed interception and correction of dosing errors Health Sciences Centre, Winnipeg, MB; Kelly https://www.ismp-canada.org/download/safetyBulletins/2016/ISMPCSB2016-02_ChangesInExpressionStrength.pdf epinephrine, there is a need to better understand the most common type of harm incident resulted from the A consumer reported receiving epinephrine by the Incident Example before they reached the patient. Current guidelines The following manufacturing deficits (which have MacKinnon, BScPharm, Clinical Pharmacist 11. Cheng A, Canadian Pediatric Society (Acute Care Committee). Emergency treatment of anaphylaxis in infants and children [position • Provide regular training using mock scenarios statement]. Paediatr Child Health 2011 [reaffirmed 2016 Feb 1];16(1):35-40. An infant weighing 6.5 kg was treated with for pediatric use of epinephrine suggest that “giving a since been addressed by the manufacturers), among (Emergency Services), Colchester East Hants Health so that healthcare providers maintain a high potential risks and problems associated with use of intravenous administration of epinephrine – either IV route, rather than the recommended IM route, as 12. EpiPen/EpiPen Jr monograph. In: e-CPS. Ottawa (ON): Canadian Pharmacists Association; [cited 2017 May 14]. Available from: degree of competency in the accurate this high-alert medication. due to selection of the incorrect route when ordering treatment for a mild allergic reaction while in the epinephrine in the emergency room for a possible dose that is slightly above the ideal dose appears to others, were reported in the analysis: Centre, Truro, NS; Dominick Shelton MD, Medical https://www.e-therapeutics.ca/search [Subscription required to access content]. preparation of an appropriate dose using the epinephrine treatment, or wrong-route administration emergency room. She experienced convulsions, anaphylactic reaction. The calculated dose, based be a better option than giving a dose that is below the Director of Quality & Safety, Emergency 13. Risk of mix-ups between ephedrine and epinephrine. ISMP Canada Saf Bull 2007 [cited 2017 Feb 2];7(2):1-3. Available from: https://www.ismp-canada.org/download/safetyBulletins/ISMPCSB2007-02Ephedrine.pdf correct concentration and safe administration A multi-incident analysis was conducted to identify (i.e., IM route ordered, but administered IV). All of angina, tachycardia, a severe headache, and on 0.01 mg/kg, should have been 0.065 mg IM; recommended dose,” given that underdosing may not Subtheme: Erroneous deployment • placement of the wrong bar code on an epinephrine Department, Sunnybrook Health Sciences Centre, 5 of epinephrine via the appropriate site. factors contributing to errors when epinephrine was the wrong-route incidents resulted in harm to the difficulty breathing. As a result, intervention and however, the infant received 0.65 mg IM, 10 times be effective to treat anaphylaxis. So for children who product Toronto, ON. used for the treatment of anaphylaxis and to suggest patients. additional monitoring were required. the intended dose. The baby became lethargic, pale, weigh close to 30 kg, practitioners may choose to Accidental or erroneous deployment of the • use of the same Drug Identification Number (DIN; Prescribers and pharmacists: strategies to prevent or minimize potential harm and cyanotic, and experienced cardiac ischemia. prescribe the ‘adult’ device, taking into account auto-injector represents the last knowledge gap used for verification in pharmacy processes) for • For pediatric prescriptions, weigh the child in when epinephrine is used for this indication. Qualitative Findings Clinical areas and teams that need to treat The child required an urgent transfer to a previous reactions and individual risk factors. subtheme. Epinephrine auto-injectors are commonly both English and French Allerject products, which kilograms at each encounter to ensure that the anaphylaxis should receive regular training, including specialized pediatric centre and prolonged carried by patients for self-administration should they led to provision of a voice-enabled device correct strength of epinephrine auto-injector Methodology Analysis revealed 3 main themes, each with multiple holding mock scenarios. Although not identified as an monitoring. Fortunately, there were no long-term Previous recommendations and actions taken by experience symptoms of anaphylaxis; however, these (intended to walk the user through the (adult versus pediatric) is being prescribed. associated subthemes (see Figure 1). This bulletin issue in this analysis, consider extending this cardiac effects. facilities to support the correct dose and route of devices can be difficult to use if patients or caregivers administration process) in an incorrect language Community pharmacy staff and managers: Reports of medication incidents related to describes each of the main themes and selected recommendation to medical office staff.5 epinephrine administration in anaphylaxis are are unfamiliar with them. For example, accidental Other pharmacy processes deemed problematic were • confusion in interpreting ratio expressions for • Review dispensary processes related to return epinephrine were extracted from voluntary reports* subthemes, along with illustrative examples. Wrong-dose and/or wrong-route errors have occurred outlined in Box 1. injection of epinephrine into the thumb of the person dispensing expired epinephrine auto-injectors and epinephrine concentration appearing on labels of products to stock and methods of verifying submitted to three ISMP Canada incident reporting when adults with anaphylaxis have been treated with administering epinephrine has occurred, likely as a failure to enter refills on prescription order entry. expiry dates. databases (Individual Practitioner Reporting, the cardiac resuscitation dose (1 mg IV) rather than Subtheme: Insufficient quantity result of a knowledge gap about device deployment. Conclusion Community Pharmacy Incident Reporting, and the recommended anaphylaxis dose (0.2 to 0.5 mg This type of incident reinforces the need for THEME: Product Flaws Consumer Reporting), and the National System for IM5).6 These errors likely result from the The subtheme of knowledge gaps regarding the practitioners to regularly confirm patients’ and Epinephrine is a critical, life-saving treatment for Incident Reporting† (NSIR) between April 2010 and comprehensive life-saving training required by quantity to be prescribed was apparent in reports in caregivers’ understanding of the proper and safe use Three brands of epinephrine auto-injector—EpiPen, anaphylaxis that can be administered by both Anaphylaxis is an acute, life-threatening, systemic October 2016. emergency practitioners, who subsequently become which too few devices were prescribed for emergency of these devices, both for therapeutic effect and to Twinject, and Allerject—were available in Canada healthcare professionals and the general public. allergic reaction associated with various triggers, more familiar with the cardiac resuscitation than the treatment of anaphylaxis in the community. Current avoid injuries. Practitioners are encouraged to use a during the period from which the data set was Because anaphylaxis can occur anywhere, workers in clinical presentations, and levels of severity.1 The following medication names were used as search anaphylaxis treatment dose of epinephrine in adults. guidelines recommend that each patient be given “teach back” method to confirm patient extracted. The latter 2 brands are no longer marketed. all healthcare sectors are encouraged to review the Epinephrine is the only life-saving drug used to treat terms: “epinephrine”, “adrenalin”, “Epipen”, 2 devices at a time, because up to 30% of anaphylaxis understanding. Common look-alike / sound-alike (LASA) incidents information identified in this analysis and implement a person experiencing anaphylaxis. Recent “Epi-pen”, “Twinject”, “Allerject”, “Anakit”, and In the current multi-incident analysis, dose-related reactions require the administration of more than were reported when prescribers confused Twinject the recommendations in this bulletin to optimize the epidemiological studies indicate that the prevalence “Ana-kit”. Almost 200 incidents were identified in incidents in the community resulted when 1 dose of epinephrine.5 In particular, for children at THEME: Process Problems with Twinrix (hepatitis A and B vaccine). Fortunately, safe and correct use of epinephrine. prescriptions were renewed for the pediatric risk of anaphylaxis, 1 device should be kept at school these errors were caught by community pharmacists * It is recognized that it is not possible to infer or project the probability of incidents on the basis of voluntary reporting systems. auto-injector when, in fact, the child’s current weight and 1 device always with the child, either on their Several reports described patients receiving an during patient counselling. † The NSIR, provided by the Canadian Institute for Health Information, is a component of the Canadian Medication Incident Reporting would require that the “adult” device be dispensed. person or with a caregiver. auto-injector device labelled with another person’s and Prevention System (CMIRPS) program. More information about the NSIR is available from: http://www.cmirps-scdpim.ca/?p=12

ISMP Canada Safety Bulletin – www.ismp-canada.org/ISMPCSafetyBulletins.htm 1 of 8 the ISMP Canada databases, and 44 were found in the THEME: Knowledge Gaps Subtheme: Wrong dose Because each device is designed to supply only a name. This situation can result when a prescription Incident Example Acknowledgements References NSIR database. Incidents not related to epinephrine single, measured dose when activated, choosing the prepared for a specific patient is returned to stock in A physician wrote a prescription for “Twinrix” with 1. Wood RA, Camargo CA Jr, Lieberman P, Sampson HA, Schwartz LB, Zitt M, et al. Anaphylaxis in America: the prevalence and use in anaphylaxis were excluded, which left 146 Subtheme: Wrong route Incorrect dose incidents with epinephrine have correct one is essential. the pharmacy, because the patient either does not pick 6 refills. The pharmacist clarified with both the ISMP Canada gratefully acknowledges the characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467. incidents in the final analysis. The analysis was occurred in both acute care and community settings. up the prescription or declines to purchase it because patient and the physician that the desired contribution of content by Waleed Alqurashi MD, 2. Tejedor-Alonso MA, Moro Moro M, Múgica-García M. Epidemiology of anaphylaxis: contributions from the last 10 years. J Investig Allergol Clin Immunol. 2015;25(3):163-175. conducted according to the methodology for For anaphylaxis, epinephrine should be administered One potential contributing factor has been use of the of cost. These types of incidents highlight problems medication was Twinject. MSc, FAAP, FRCPC, Assistant Professor, University 3. Anaphylaxis and allergy in the emergency department.Ottawa (ON): Canadian Institute for Health Information; 2015 Sep 10 [cited multi-incident analysis outlined in the Canadian intramuscularly (IM); the intravenous (IV) route of historical ratio expressions (1:1000, 1:10,000) for in 2 community pharmacy processes—the process to of Ottawa Department of Pediatrics and Emergency 2017 Mar 20]. Available from: https://secure.cihi.ca/free_products/Anaphylaxis_Infosheet_en.pdf Incident Analysis Framework.4 administration should be reserved for patients who strength. In 2016, because of an ongoing stream of return a product to stock, and the dispensing process LASA issues were also reported from the hospital Medicine Children’s Hospital of Eastern Ontario 4. Incident Analysis Collaborating Parties. Canadian incident analysis framework. Edmonton (AB): Canadian Patient Safety Institute; have not responded to IM doses and those serious errors related to confusion in understanding for labelling and verification of both the outer setting, where ePHEDrine was mistaken for (CHEO), ON and Ken J Farion MD FRCPC, Medical 2012 [cited 2016 Nov 14]. Incident Analysis Collaborating Parties are Canadian Patient Safety Institute (CPSI), Institute for Safe Quantitative Findings experiencing severe physiologic compromise.5 ratio expressions, the United States Pharmacopoeia packaging and the device inside the box. epinephrine when medication vials were being Director – Quality & Systems Improvement, Medication Practices Canada, Saskatchewan Health, Patients for Patient Safety Canada (a patient-led program of CPSI), Paula Beard, Carolyn E. Hoffman, and Micheline Ste-Marie. Available from: http://www.patientsafetyinstitute.ca/en/toolsResources/Incident Wrong-route administration of epinephrine has been eliminated ratio expressions on single-entity drug re-stocked. Children’s Hospital of Eastern Ontario, Ottawa, ON Analysis/Documents/Canadian%20Incident%20Analysis%20Framework.PDF The majority of the incidents were reported to the previously reported in an ISMP Canada Safety products such as epinephrine.10 Therefore, 1:1000 Incident Example and acknowledges the following individuals for their 5. Lieberman P, Nicklas RA, Randolph C, Oppenheimer J, Bernstein D, Ellis A et al. Anaphylaxis—a practice parameter update 2015. ISMP Canada databases. Of these reports, wrong Bulletin6 and elsewhere in the literature.7,8 In a review epinephrine products are now labelled as 1 mg/mL, An Epi-Pen was dispensed for a child. The expert review of this bulletin: Ann Allergy Asthma Immunol. 2015;115(5):341-384. dose errors (e.g., Epipen Jr. given to a child weighing of more than 600 cases reported to the Pennsylvania while epinephrine 1:10,000 for IV injection is caregiver at school noticed that the device was 6. Alert: wrong route incidents with epinephrine. ISMP Canada Saf Bull 2014 [cited 2017 Feb 2];14(4):1-3. Available from: https://www.ismp-canada.org/download/safetyBulletins/2014/ISMPCSB2014-4_Epinephrine.pdf 30 kg or greater) comprised the most commonly Patient Safety Reporting System, wrong-route errors labelled as 0.1 mg/mL. A second potential factor labelled with someone else’s name, even though the Waleed Alqurashi MD, MSc, FAAP, FRCPC, 7. Campbell RL, Bellolio MF, Knutson BD, Bellamkonda VR, Fedko MG, Nestler DM, et al. Epinephrine in anaphylaxis: higher risk of reported incident type, followed by products being involving IV administration were responsible for contributing to incorrect dosing is the need for a dose Pediatric devices contain an epinephrine dose outer box was labelled correctly. The school Assistant Professor, University of Ottawa Department cardiovascular complications and overdose after administration of intravenous bolus epinephrine compared with intramuscular of anaphylaxis is increasing.2,3 The Canadian Institute prepared for the wrong patient and wrong quantity 25.4% of all epinephrine adverse events and 63.3% of calculation in the pediatric age group. The appropriate for a child weighing between 15 to 30 kg notified the parents, who contacted the pharmacy. of Pediatrics and Emergency Medicine Children’s epinephrine. J Allergy Clin Immunol Pract. 2015;3(1):76-80. for Health Information (CIHI) reported that from dispensed. Over 80% of incidents were caught before the harmful events.8 Several studies have attributed epinephrine dose for anaphylaxis in pediatrics must (i.e., 0.15 mg); the ‘adult’ device delivers 0.3 mg and The pharmacy determined that the device provided Hospital of Eastern Ontario (CHEO), ON; Stephanie 8. An update on the “Epi”demic: events involving EPINEPHrine. Pa Patient Saf Advis. 2009;6(3):102-103. 2006 to 2015, there was a 64% increase in the the error reached the patient. this error to a lack of adequate education of be calculated according to the patient’s weight is recommended for children (and adults) weighing for the child had previously been returned to stock Crampton, RN, BSN, ENC(C), Cornwall Hospital, 9. Cohen MB, Saunders SS, Wise SK, Nassif S, Platt MP. Pitfalls in the use of epinephrine for anaphylaxis: patient and provider 9 11 12 opportunities for improvement. Int Forum Allergy Rhinol. 2017;7(3):276-286. number of individuals for whom an epinephrine healthcare professionals. (0.01 mg/kg, up to a maximum of 0.5 mg); this 30 kg or more. In several of the incidents analyzed, without removal of the old label. Cornwall, ON; Tracy Furst, BSc, BScPharm, 10. Changes in expression of strength: elimination of ratios on single-entity injectable products. ISMP Can Saf Bull 2016 [cited 2017 auto-injector was dispensed, and children were the Of the incidents reported to ISMP Canada databases, calculation step represents a risk for error. verification of the child’s weight at the pharmacy Children's Emergency Department Pharmacist, Feb 12]; 16(2):1-3. Available from: top consumers.3 Because of the increased use of 3.5% of cases resulted in harm to the patient. The Incident Example allowed interception and correction of dosing errors Health Sciences Centre, Winnipeg, MB; Kelly https://www.ismp-canada.org/download/safetyBulletins/2016/ISMPCSB2016-02_ChangesInExpressionStrength.pdf epinephrine, there is a need to better understand the most common type of harm incident resulted from the A consumer reported receiving epinephrine by the Incident Example before they reached the patient. Current guidelines The following manufacturing deficits (which have MacKinnon, BScPharm, Clinical Pharmacist 11. Cheng A, Canadian Pediatric Society (Acute Care Committee). Emergency treatment of anaphylaxis in infants and children [position statement]. Paediatr Child Health 2011 [reaffirmed 2016 Feb 1];16(1):35-40. potential risks and problems associated with use of intravenous administration of epinephrine – either IV route, rather than the recommended IM route, as An infant weighing 6.5 kg was treated with for pediatric use of epinephrine suggest that “giving a since been addressed by the manufacturers), among (Emergency Services), Colchester East Hants Health 12. EpiPen/EpiPen Jr monograph. In: e-CPS. Ottawa (ON): Canadian Pharmacists Association; [cited 2017 May 14]. Available from: this high-alert medication. due to selection of the incorrect route when ordering treatment for a mild allergic reaction while in the epinephrine in the emergency room for a possible dose that is slightly above the ideal dose appears to others, were reported in the analysis: Centre, Truro, NS; Dominick Shelton MD, Medical https://www.e-therapeutics.ca/search [Subscription required to access content]. epinephrine treatment, or wrong-route administration emergency room. She experienced convulsions, anaphylactic reaction. The calculated dose, based be a better option than giving a dose that is below the Director of Quality & Safety, Emergency 13. Risk of mix-ups between ephedrine and epinephrine. ISMP Canada Saf Bull 2007 [cited 2017 Feb 2];7(2):1-3. Available from: A multi-incident analysis was conducted to identify (i.e., IM route ordered, but administered IV). All of angina, tachycardia, a severe headache, and on 0.01 mg/kg, should have been 0.065 mg IM; recommended dose,” given that underdosing may not Subtheme: Erroneous deployment • placement of the wrong bar code on an epinephrine Department, Sunnybrook Health Sciences Centre, https://www.ismp-canada.org/download/safetyBulletins/ISMPCSB2007-02Ephedrine.pdf factors contributing to errors when epinephrine was the wrong-route incidents resulted in harm to the difficulty breathing. As a result, intervention and however, the infant received 0.65 mg IM, 10 times be effective to treat anaphylaxis.5 So for children who product Toronto, ON. used for the treatment of anaphylaxis and to suggest patients. additional monitoring were required. the intended dose. The baby became lethargic, pale, weigh close to 30 kg, practitioners may choose to Accidental or erroneous deployment of the • use of the same Drug Identification Number (DIN; strategies to prevent or minimize potential harm and cyanotic, and experienced cardiac ischemia. prescribe the ‘adult’ device, taking into account auto-injector represents the last knowledge gap used for verification in pharmacy processes) for when epinephrine is used for this indication. Qualitative Findings Clinical areas and teams that need to treat The child required an urgent transfer to a previous reactions and individual risk factors. subtheme. Epinephrine auto-injectors are commonly both English and French Allerject products, which anaphylaxis should receive regular training, including specialized pediatric centre and prolonged carried by patients for self-administration should they led to provision of a voice-enabled device Methodology Analysis revealed 3 main themes, each with multiple holding mock scenarios. Although not identified as an monitoring. Fortunately, there were no long-term Previous recommendations and actions taken by experience symptoms of anaphylaxis; however, these (intended to walk the user through the associated subthemes (see Figure 1). This bulletin issue in this analysis, consider extending this cardiac effects. facilities to support the correct dose and route of devices can be difficult to use if patients or caregivers administration process) in an incorrect language Reports of medication incidents related to describes each of the main themes and selected recommendation to medical office staff.5 epinephrine administration in anaphylaxis are are unfamiliar with them. For example, accidental Other pharmacy processes deemed problematic were • confusion in interpreting ratio expressions for epinephrine were extracted from voluntary reports* subthemes, along with illustrative examples. Wrong-dose and/or wrong-route errors have occurred outlined in Box 1. injection of epinephrine into the thumb of the person dispensing expired epinephrine auto-injectors and epinephrine concentration appearing on labels submitted to three ISMP Canada incident reporting when adults with anaphylaxis have been treated with administering epinephrine has occurred, likely as a failure to enter refills on prescription order entry. databases (Individual Practitioner Reporting, the cardiac resuscitation dose (1 mg IV) rather than Subtheme: Insufficient quantity result of a knowledge gap about device deployment. Conclusion Community Pharmacy Incident Reporting, and Figure 1. Main themes from the qualitative analysis the recommended anaphylaxis dose (0.2 to 0.5 mg This type of incident reinforces the need for THEME: Product Flaws Consumer Reporting), and the National System for IM5).6 These errors likely result from the The subtheme of knowledge gaps regarding the practitioners to regularly confirm patients’ and Epinephrine is a critical, life-saving treatment for Incident Reporting† (NSIR) between April 2010 and comprehensive life-saving training required by quantity to be prescribed was apparent in reports in caregivers’ understanding of the proper and safe use Three brands of epinephrine auto-injector—EpiPen, anaphylaxis that can be administered by both Anaphylaxis is an acute, life-threatening, systemic October 2016. emergency practitioners, who subsequently become which too few devices were prescribed for emergency of these devices, both for therapeutic effect and to Twinject, and Allerject—were available in Canada healthcare professionals and the general public. allergic reaction associated with various triggers, more familiar with the cardiac resuscitation than the treatment of anaphylaxis in the community. Current avoid injuries. Practitioners are encouraged to use a during the period from which the data set was Because anaphylaxis can occur anywhere, workers in clinical presentations, and levels of severity.1 The following medication names were used as search anaphylaxis treatment dose of epinephrine in adults. guidelines recommend that each patient be given “teach back” method to confirm patient extracted. The latter 2 brands are no longer marketed. all healthcare sectors are encouraged to review the Epinephrine is the only life-saving drug used to treat terms: “epinephrine”, “adrenalin”, “Epipen”, 2 devices at a time, because up to 30% of anaphylaxis understanding. Common look-alike / sound-alike (LASA) incidents information identified in this analysis and implement a person experiencing anaphylaxis. Recent “Epi-pen”, “Twinject”, “Allerject”, “Anakit”, and In the current multi-incident analysis, dose-related reactions require the administration of more than were reported when prescribers confused Twinject the recommendations in this bulletin to optimize the 5 epidemiological studies indicate that the prevalence “Ana-kit”. Almost 200 incidents were identified in • Wrong route • Return to stock • Look-alike / sound-alike names incidents in the community resulted when 1 dose of epinephrine. In particular, for children at THEME: Process Problems with Twinrix (hepatitis A and B vaccine). Fortunately, safe and correct use of epinephrine. • Wrong dose • Identification of expired products • Product defects prescriptions were renewed for the pediatric risk of anaphylaxis, 1 device should be kept at school these errors were caught by community pharmacists • Insufficient quantity • Orders for refills missed auto-injector when, in fact, the child’s current weight and 1 device always with the child, either on their Several reports described patients receiving an during patient counselling. • Erroneous deployment would require that the “adult” device be dispensed. person or with a caregiver. auto-injector device labelled with another person’s

ISMP Canada Safety Bulletin – Volume 17 • Issue 6 • June 29 , 2017 2 of 8 the ISMP Canada databases, and 44 were found in the THEME: Knowledge Gaps Subtheme: Wrong dose Because each device is designed to supply only a name. This situation can result when a prescription Incident Example Acknowledgements References NSIR database. Incidents not related to epinephrine single, measured dose when activated, choosing the prepared for a specific patient is returned to stock in A physician wrote a prescription for “Twinrix” with 1. Wood RA, Camargo CA Jr, Lieberman P, Sampson HA, Schwartz LB, Zitt M, et al. Anaphylaxis in America: the prevalence and use in anaphylaxis were excluded, which left 146 Subtheme: Wrong route Incorrect dose incidents with epinephrine have correct one is essential. the pharmacy, because the patient either does not pick 6 refills. The pharmacist clarified with both the ISMP Canada gratefully acknowledges the characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467. incidents in the final analysis. The analysis was occurred in both acute care and community settings. up the prescription or declines to purchase it because patient and the physician that the desired contribution of content by Waleed Alqurashi MD, 2. Tejedor-Alonso MA, Moro Moro M, Múgica-García M. Epidemiology of anaphylaxis: contributions from the last 10 years. J Investig Allergol Clin Immunol. 2015;25(3):163-175. conducted according to the methodology for For anaphylaxis, epinephrine should be administered One potential contributing factor has been use of the of cost. These types of incidents highlight problems medication was Twinject. MSc, FAAP, FRCPC, Assistant Professor, University 3. Anaphylaxis and allergy in the emergency department.Ottawa (ON): Canadian Institute for Health Information; 2015 Sep 10 [cited multi-incident analysis outlined in the Canadian intramuscularly (IM); the intravenous (IV) route of historical ratio expressions (1:1000, 1:10,000) for in 2 community pharmacy processes—the process to of Ottawa Department of Pediatrics and Emergency 2017 Mar 20]. Available from: https://secure.cihi.ca/free_products/Anaphylaxis_Infosheet_en.pdf Incident Analysis Framework.4 administration should be reserved for patients who strength. In 2016, because of an ongoing stream of return a product to stock, and the dispensing process LASA issues were also reported from the hospital Medicine Children’s Hospital of Eastern Ontario 4. Incident Analysis Collaborating Parties. Canadian incident analysis framework. Edmonton (AB): Canadian Patient Safety Institute; have not responded to IM doses and those serious errors related to confusion in understanding for labelling and verification of both the outer setting, where ePHEDrine was mistaken for (CHEO), ON and Ken J Farion MD FRCPC, Medical 2012 [cited 2016 Nov 14]. Incident Analysis Collaborating Parties are Canadian Patient Safety Institute (CPSI), Institute for Safe Quantitative Findings experiencing severe physiologic compromise.5 ratio expressions, the United States Pharmacopoeia packaging and the device inside the box. epinephrine when medication vials were being Director – Quality & Systems Improvement, Medication Practices Canada, Saskatchewan Health, Patients for Patient Safety Canada (a patient-led program of CPSI), Paula Beard, Carolyn E. Hoffman, and Micheline Ste-Marie. Available from: http://www.patientsafetyinstitute.ca/en/toolsResources/Incident Wrong-route administration of epinephrine has been eliminated ratio expressions on single-entity drug re-stocked. Children’s Hospital of Eastern Ontario, Ottawa, ON Analysis/Documents/Canadian%20Incident%20Analysis%20Framework.PDF The majority of the incidents were reported to the previously reported in an ISMP Canada Safety products such as epinephrine.10 Therefore, 1:1000 Incident Example and acknowledges the following individuals for their 5. Lieberman P, Nicklas RA, Randolph C, Oppenheimer J, Bernstein D, Ellis A et al. Anaphylaxis—a practice parameter update 2015. ISMP Canada databases. Of these reports, wrong Bulletin6 and elsewhere in the literature.7,8 In a review epinephrine products are now labelled as 1 mg/mL, An Epi-Pen was dispensed for a child. The expert review of this bulletin: Ann Allergy Asthma Immunol. 2015;115(5):341-384. dose errors (e.g., Epipen Jr. given to a child weighing of more than 600 cases reported to the Pennsylvania while epinephrine 1:10,000 for IV injection is caregiver at school noticed that the device was 6. Alert: wrong route incidents with epinephrine. ISMP Canada Saf Bull 2014 [cited 2017 Feb 2];14(4):1-3. Available from: https://www.ismp-canada.org/download/safetyBulletins/2014/ISMPCSB2014-4_Epinephrine.pdf 30 kg or greater) comprised the most commonly Patient Safety Reporting System, wrong-route errors labelled as 0.1 mg/mL. A second potential factor labelled with someone else’s name, even though the Waleed Alqurashi MD, MSc, FAAP, FRCPC, 7. Campbell RL, Bellolio MF, Knutson BD, Bellamkonda VR, Fedko MG, Nestler DM, et al. Epinephrine in anaphylaxis: higher risk of reported incident type, followed by products being involving IV administration were responsible for contributing to incorrect dosing is the need for a dose Pediatric devices contain an epinephrine dose outer box was labelled correctly. The school Assistant Professor, University of Ottawa Department cardiovascular complications and overdose after administration of intravenous bolus epinephrine compared with intramuscular of anaphylaxis is increasing.2,3 The Canadian Institute prepared for the wrong patient and wrong quantity 25.4% of all epinephrine adverse events and 63.3% of calculation in the pediatric age group. The appropriate for a child weighing between 15 to 30 kg notified the parents, who contacted the pharmacy. of Pediatrics and Emergency Medicine Children’s epinephrine. J Allergy Clin Immunol Pract. 2015;3(1):76-80. for Health Information (CIHI) reported that from dispensed. Over 80% of incidents were caught before the harmful events.8 Several studies have attributed epinephrine dose for anaphylaxis in pediatrics must (i.e., 0.15 mg); the ‘adult’ device delivers 0.3 mg and The pharmacy determined that the device provided Hospital of Eastern Ontario (CHEO), ON; Stephanie 8. An update on the “Epi”demic: events involving EPINEPHrine. Pa Patient Saf Advis. 2009;6(3):102-103. 2006 to 2015, there was a 64% increase in the the error reached the patient. this error to a lack of adequate education of be calculated according to the patient’s weight is recommended for children (and adults) weighing for the child had previously been returned to stock Crampton, RN, BSN, ENC(C), Cornwall Hospital, 9. Cohen MB, Saunders SS, Wise SK, Nassif S, Platt MP. Pitfalls in the use of epinephrine for anaphylaxis: patient and provider 9 11 12 opportunities for improvement. Int Forum Allergy Rhinol. 2017;7(3):276-286. number of individuals for whom an epinephrine healthcare professionals. (0.01 mg/kg, up to a maximum of 0.5 mg); this 30 kg or more. In several of the incidents analyzed, without removal of the old label. Cornwall, ON; Tracy Furst, BSc, BScPharm, 10. Changes in expression of strength: elimination of ratios on single-entity injectable products. ISMP Can Saf Bull 2016 [cited 2017 auto-injector was dispensed, and children were the Of the incidents reported to ISMP Canada databases, calculation step represents a risk for error. verification of the child’s weight at the pharmacy Children's Emergency Department Pharmacist, Feb 12]; 16(2):1-3. Available from: top consumers.3 Because of the increased use of 3.5% of cases resulted in harm to the patient. The Incident Example allowed interception and correction of dosing errors Health Sciences Centre, Winnipeg, MB; Kelly https://www.ismp-canada.org/download/safetyBulletins/2016/ISMPCSB2016-02_ChangesInExpressionStrength.pdf epinephrine, there is a need to better understand the most common type of harm incident resulted from the A consumer reported receiving epinephrine by the Incident Example before they reached the patient. Current guidelines The following manufacturing deficits (which have MacKinnon, BScPharm, Clinical Pharmacist 11. Cheng A, Canadian Pediatric Society (Acute Care Committee). Emergency treatment of anaphylaxis in infants and children [position statement]. Paediatr Child Health 2011 [reaffirmed 2016 Feb 1];16(1):35-40. potential risks and problems associated with use of intravenous administration of epinephrine – either IV route, rather than the recommended IM route, as An infant weighing 6.5 kg was treated with for pediatric use of epinephrine suggest that “giving a since been addressed by the manufacturers), among (Emergency Services), Colchester East Hants Health 12. EpiPen/EpiPen Jr monograph. In: e-CPS. Ottawa (ON): Canadian Pharmacists Association; [cited 2017 May 14]. Available from: this high-alert medication. due to selection of the incorrect route when ordering treatment for a mild allergic reaction while in the epinephrine in the emergency room for a possible dose that is slightly above the ideal dose appears to others, were reported in the analysis: Centre, Truro, NS; Dominick Shelton MD, Medical https://www.e-therapeutics.ca/search [Subscription required to access content]. epinephrine treatment, or wrong-route administration emergency room. She experienced convulsions, anaphylactic reaction. The calculated dose, based be a better option than giving a dose that is below the Director of Quality & Safety, Emergency 13. Risk of mix-ups between ephedrine and epinephrine. ISMP Canada Saf Bull 2007 [cited 2017 Feb 2];7(2):1-3. Available from: A multi-incident analysis was conducted to identify (i.e., IM route ordered, but administered IV). All of angina, tachycardia, a severe headache, and on 0.01 mg/kg, should have been 0.065 mg IM; recommended dose,” given that underdosing may not Subtheme: Erroneous deployment • placement of the wrong bar code on an epinephrine Department, Sunnybrook Health Sciences Centre, https://www.ismp-canada.org/download/safetyBulletins/ISMPCSB2007-02Ephedrine.pdf factors contributing to errors when epinephrine was the wrong-route incidents resulted in harm to the difficulty breathing. As a result, intervention and however, the infant received 0.65 mg IM, 10 times be effective to treat anaphylaxis.5 So for children who product Toronto, ON. used for the treatment of anaphylaxis and to suggest patients. additional monitoring were required. the intended dose. The baby became lethargic, pale, weigh close to 30 kg, practitioners may choose to Accidental or erroneous deployment of the • use of the same Drug Identification Number (DIN; strategies to prevent or minimize potential harm and cyanotic, and experienced cardiac ischemia. prescribe the ‘adult’ device, taking into account auto-injector represents the last knowledge gap used for verification in pharmacy processes) for when epinephrine is used for this indication. Qualitative Findings Clinical areas and teams that need to treat The child required an urgent transfer to a previous reactions and individual risk factors. subtheme. Epinephrine auto-injectors are commonly both English and French Allerject products, which anaphylaxis should receive regular training, including specialized pediatric centre and prolonged carried by patients for self-administration should they led to provision of a voice-enabled device Methodology Analysis revealed 3 main themes, each with multiple holding mock scenarios. Although not identified as an monitoring. Fortunately, there were no long-term Previous recommendations and actions taken by experience symptoms of anaphylaxis; however, these (intended to walk the user through the associated subthemes (see Figure 1). This bulletin issue in this analysis, consider extending this cardiac effects. facilities to support the correct dose and route of devices can be difficult to use if patients or caregivers administration process) in an incorrect language Reports of medication incidents related to describes each of the main themes and selected recommendation to medical office staff.5 epinephrine administration in anaphylaxis are are unfamiliar with them. For example, accidental Other pharmacy processes deemed problematic were • confusion in interpreting ratio expressions for epinephrine were extracted from voluntary reports* subthemes, along with illustrative examples. Wrong-dose and/or wrong-route errors have occurred outlined in Box 1. injection of epinephrine into the thumb of the person dispensing expired epinephrine auto-injectors and epinephrine concentration appearing on labels submitted to three ISMP Canada incident reporting when adults with anaphylaxis have been treated with administering epinephrine has occurred, likely as a failure to enter refills on prescription order entry. databases (Individual Practitioner Reporting, the cardiac resuscitation dose (1 mg IV) rather than Subtheme: Insufficient quantity result of a knowledge gap about device deployment. Conclusion Community Pharmacy Incident Reporting, and the recommended anaphylaxis dose (0.2 to 0.5 mg This type of incident reinforces the need for THEME: Product Flaws Consumer Reporting), and the National System for IM5).6 These errors likely result from the The subtheme of knowledge gaps regarding the practitioners to regularly confirm patients’ and Epinephrine is a critical, life-saving treatment for Incident Reporting† (NSIR) between April 2010 and comprehensive life-saving training required by quantity to be prescribed was apparent in reports in caregivers’ understanding of the proper and safe use Three brands of epinephrine auto-injector—EpiPen, anaphylaxis that can be administered by both Anaphylaxis is an acute, life-threatening, systemic October 2016. emergency practitioners, who subsequently become which too few devices were prescribed for emergency of these devices, both for therapeutic effect and to Twinject, and Allerject—were available in Canada healthcare professionals and the general public. allergic reaction associated with various triggers, more familiar with the cardiac resuscitation than the treatment of anaphylaxis in the community. Current avoid injuries. Practitioners are encouraged to use a during the period from which the data set was Because anaphylaxis can occur anywhere, workers in clinical presentations, and levels of severity.1 The following medication names were used as search anaphylaxis treatment dose of epinephrine in adults. guidelines recommend that each patient be given “teach back” method to confirm patient extracted. The latter 2 brands are no longer marketed. all healthcare sectors are encouraged to review the Epinephrine is the only life-saving drug used to treat terms: “epinephrine”, “adrenalin”, “Epipen”, 2 devices at a time, because up to 30% of anaphylaxis understanding. Common look-alike / sound-alike (LASA) incidents information identified in this analysis and implement a person experiencing anaphylaxis. Recent “Epi-pen”, “Twinject”, “Allerject”, “Anakit”, and In the current multi-incident analysis, dose-related reactions require the administration of more than were reported when prescribers confused Twinject the recommendations in this bulletin to optimize the epidemiological studies indicate that the prevalence “Ana-kit”. Almost 200 incidents were identified in incidents in the community resulted when 1 dose of epinephrine.5 In particular, for children at THEME: Process Problems with Twinrix (hepatitis A and B vaccine). Fortunately, safe and correct use of epinephrine. prescriptions were renewed for the pediatric risk of anaphylaxis, 1 device should be kept at school these errors were caught by community pharmacists auto-injector when, in fact, the child’s current weight and 1 device always with the child, either on their Several reports described patients receiving an during patient counselling. would require that the “adult” device be dispensed. person or with a caregiver. auto-injector device labelled with another person’s

ISMP Canada Safety Bulletin – Volume 17 • Issue 6 • June 29, 2017 3 of 8 the ISMP Canada databases, and 44 were found in the THEME: Knowledge Gaps Subtheme: Wrong dose Because each device is designed to supply only a Box 1. Measures taken to support correct dose and name. This situation can result when a prescription Incident Example Acknowledgements References 6 NSIR database. Incidents not related to epinephrine single, measured dose when activated, choosing the route for epinephrine injection prepared for a specific patient is returned to stock in A physician wrote a prescription for “Twinrix” with 1. Wood RA, Camargo CA Jr, Lieberman P, Sampson HA, Schwartz LB, Zitt M, et al. Anaphylaxis in America: the prevalence and use in anaphylaxis were excluded, which left 146 Subtheme: Wrong route Incorrect dose incidents with epinephrine have correct one is essential. the pharmacy, because the patient either does not pick 6 refills. The pharmacist clarified with both the ISMP Canada gratefully acknowledges the characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467. incidents in the final analysis. The analysis was occurred in both acute care and community settings. up the prescription or declines to purchase it because patient and the physician that the desired contribution of content by Waleed Alqurashi MD, 2. Tejedor-Alonso MA, Moro Moro M, Múgica-García M. Epidemiology of anaphylaxis: contributions from the last 10 years. J Investig Allergol Clin Immunol. 2015;25(3):163-175. conducted according to the methodology for For anaphylaxis, epinephrine should be administered One potential contributing factor has been use of the • provision of epinephrine auto-injectors of cost. These types of incidents highlight problems medication was Twinject. MSc, FAAP, FRCPC, Assistant Professor, University or prepackaged epinephrine for IM use, 3. Anaphylaxis and allergy in the emergency department.Ottawa (ON): Canadian Institute for Health Information; 2015 Sep 10 [cited multi-incident analysis outlined in the Canadian intramuscularly (IM); the intravenous (IV) route of historical ratio expressions (1:1000, 1:10,000) for in 2 community pharmacy processes—the process to of Ottawa Department of Pediatrics and Emergency 2017 Mar 20]. Available from: https://secure.cihi.ca/free_products/Anaphylaxis_Infosheet_en.pdf 4 together with instructions for IM use, at Incident Analysis Framework. administration should be reserved for patients who strength. In 2016, because of an ongoing stream of the point of care return a product to stock, and the dispensing process LASA issues were also reported from the hospital Medicine Children’s Hospital of Eastern Ontario 4. Incident Analysis Collaborating Parties. Canadian incident analysis framework. Edmonton (AB): Canadian Patient Safety Institute; 2012 [cited 2016 Nov 14]. Incident Analysis Collaborating Parties are Canadian Patient Safety Institute (CPSI), Institute for Safe have not responded to IM doses and those serious errors related to confusion in understanding • written reminders (e.g., a dosing chart) in for labelling and verification of both the outer setting, where ePHEDrine was mistaken for (CHEO), ON and Ken J Farion MD FRCPC, Medical Quantitative Findings experiencing severe physiologic compromise.5 ratio expressions, the United States Pharmacopoeia packaging and the device inside the box. epinephrine when medication vials were being Director – Quality & Systems Improvement, Medication Practices Canada, Saskatchewan Health, Patients for Patient Safety Canada (a patient-led program of CPSI), Paula Beard, all locations where epinephrine is Carolyn E. Hoffman, and Micheline Ste-Marie. Available from: http://www.patientsafetyinstitute.ca/en/toolsResources/Incident Wrong-route administration of epinephrine has been eliminated ratio expressions on single-entity drug stocked re-stocked. Children’s Hospital of Eastern Ontario, Ottawa, ON Analysis/Documents/Canadian%20Incident%20Analysis%20Framework.PDF The majority of the incidents were reported to the previously reported in an ISMP Canada Safety products such as epinephrine.10 Therefore, 1:1000 • separated storage of epinephrine Incident Example and acknowledges the following individuals for their 5. Lieberman P, Nicklas RA, Randolph C, Oppenheimer J, Bernstein D, Ellis A et al. Anaphylaxis—a practice parameter update 2015. ISMP Canada databases. Of these reports, wrong Bulletin6 and elsewhere in the literature.7,8 In a review epinephrine products are now labelled as 1 mg/mL, products used for the treatment of An Epi-Pen was dispensed for a child. The expert review of this bulletin: Ann Allergy Asthma Immunol. 2015;115(5):341-384. dose errors (e.g., Epipen Jr. given to a child weighing of more than 600 cases reported to the Pennsylvania while epinephrine 1:10,000 for IV injection is anaphylaxis from those epinephrine caregiver at school noticed that the device was 6. Alert: wrong route incidents with epinephrine. ISMP Canada Saf Bull 2014 [cited 2017 Feb 2];14(4):1-3. Available from: products intended for resuscitation carts https://www.ismp-canada.org/download/safetyBulletins/2014/ISMPCSB2014-4_Epinephrine.pdf 30 kg or greater) comprised the most commonly Patient Safety Reporting System, wrong-route errors labelled as 0.1 mg/mL. A second potential factor labelled with someone else’s name, even though the Waleed Alqurashi MD, MSc, FAAP, FRCPC, 7. Campbell RL, Bellolio MF, Knutson BD, Bellamkonda VR, Fedko MG, Nestler DM, et al. Epinephrine in anaphylaxis: higher risk of • use of preprinted order sets for the reported incident type, followed by products being involving IV administration were responsible for contributing to incorrect dosing is the need for a dose Pediatric devices contain an epinephrine dose outer box was labelled correctly. The school Assistant Professor, University of Ottawa Department cardiovascular complications and overdose after administration of intravenous bolus epinephrine compared with intramuscular of anaphylaxis is increasing.2,3 The Canadian Institute prepared for the wrong patient and wrong quantity 25.4% of all epinephrine adverse events and 63.3% of calculation in the pediatric age group. The appropriate for a child weighing between 15 to 30 kg management of anaphylaxis notified the parents, who contacted the pharmacy. of Pediatrics and Emergency Medicine Children’s epinephrine. J Allergy Clin Immunol Pract. 2015;3(1):76-80. for Health Information (CIHI) reported that from dispensed. Over 80% of incidents were caught before the harmful events.8 Several studies have attributed epinephrine dose for anaphylaxis in pediatrics must (i.e., 0.15 mg); the ‘adult’ device delivers 0.3 mg and • minimize use of verbal orders; if verbal The pharmacy determined that the device provided Hospital of Eastern Ontario (CHEO), ON; Stephanie 8. An update on the “Epi”demic: events involving EPINEPHrine. Pa Patient Saf Advis. 2009;6(3):102-103. orders are needed in emergency 2006 to 2015, there was a 64% increase in the the error reached the patient. this error to a lack of adequate education of be calculated according to the patient’s weight is recommended for children (and adults) weighing for the child had previously been returned to stock Crampton, RN, BSN, ENC(C), Cornwall Hospital, 9. Cohen MB, Saunders SS, Wise SK, Nassif S, Platt MP. Pitfalls in the use of epinephrine for anaphylaxis: patient and provider situations, use a “repeat back” or “closed opportunities for improvement. Int Forum Allergy Rhinol. 2017;7(3):276-286. 9 11 30 kg or more.12 In several of the incidents analyzed, without removal of the old label. number of individuals for whom an epinephrine healthcare professionals. (0.01 mg/kg, up to a maximum of 0.5 mg); this loop communication” strategy to confirm Cornwall, ON; Tracy Furst, BSc, BScPharm, 10. Changes in expression of strength: elimination of ratios on single-entity injectable products. ISMP Can Saf Bull 2016 [cited 2017 auto-injector was dispensed, and children were the Of the incidents reported to ISMP Canada databases, calculation step represents a risk for error. verification of the child’s weight at the pharmacy drug name, dose, and route of Children's Emergency Department Pharmacist, Feb 12]; 16(2):1-3. Available from: 3 top consumers. Because of the increased use of 3.5% of cases resulted in harm to the patient. The Incident Example allowed interception and correction of dosing errors administration Health Sciences Centre, Winnipeg, MB; Kelly https://www.ismp-canada.org/download/safetyBulletins/2016/ISMPCSB2016-02_ChangesInExpressionStrength.pdf epinephrine, there is a need to better understand the most common type of harm incident resulted from the A consumer reported receiving epinephrine by the Incident Example before they reached the patient. Current guidelines The following manufacturing deficits (which have MacKinnon, BScPharm, Clinical Pharmacist 11. Cheng A, Canadian Pediatric Society (Acute Care Committee). Emergency treatment of anaphylaxis in infants and children [position statement]. Paediatr Child Health 2011 [reaffirmed 2016 Feb 1];16(1):35-40. potential risks and problems associated with use of intravenous administration of epinephrine – either IV route, rather than the recommended IM route, as An infant weighing 6.5 kg was treated with for pediatric use of epinephrine suggest that “giving a since been addressed by the manufacturers), among (Emergency Services), Colchester East Hants Health 12. EpiPen/EpiPen Jr monograph. In: e-CPS. Ottawa (ON): Canadian Pharmacists Association; [cited 2017 May 14]. Available from: this high-alert medication. due to selection of the incorrect route when ordering treatment for a mild allergic reaction while in the epinephrine in the emergency room for a possible dose that is slightly above the ideal dose appears to others, were reported in the analysis: Centre, Truro, NS; Dominick Shelton MD, Medical https://www.e-therapeutics.ca/search [Subscription required to access content]. epinephrine treatment, or wrong-route administration emergency room. She experienced convulsions, anaphylactic reaction. The calculated dose, based be a better option than giving a dose that is below the Director of Quality & Safety, Emergency 13. Risk of mix-ups between ephedrine and epinephrine. ISMP Canada Saf Bull 2007 [cited 2017 Feb 2];7(2):1-3. Available from: A multi-incident analysis was conducted to identify (i.e., IM route ordered, but administered IV). All of angina, tachycardia, a severe headache, and on 0.01 mg/kg, should have been 0.065 mg IM; recommended dose,” given that underdosing may not Subtheme: Erroneous deployment • placement of the wrong bar code on an epinephrine Department, Sunnybrook Health Sciences Centre, https://www.ismp-canada.org/download/safetyBulletins/ISMPCSB2007-02Ephedrine.pdf factors contributing to errors when epinephrine was the wrong-route incidents resulted in harm to the difficulty breathing. As a result, intervention and however, the infant received 0.65 mg IM, 10 times be effective to treat anaphylaxis.5 So for children who product Toronto, ON. used for the treatment of anaphylaxis and to suggest patients. additional monitoring were required. the intended dose. The baby became lethargic, pale, weigh close to 30 kg, practitioners may choose to Accidental or erroneous deployment of the • use of the same Drug Identification Number (DIN; strategies to prevent or minimize potential harm and cyanotic, and experienced cardiac ischemia. prescribe the ‘adult’ device, taking into account auto-injector represents the last knowledge gap used for verification in pharmacy processes) for when epinephrine is used for this indication. Qualitative Findings Clinical areas and teams that need to treat The child required an urgent transfer to a previous reactions and individual risk factors. subtheme. Epinephrine auto-injectors are commonly both English and French Allerject products, which anaphylaxis should receive regular training, including specialized pediatric centre and prolonged carried by patients for self-administration should they led to provision of a voice-enabled device Methodology Analysis revealed 3 main themes, each with multiple holding mock scenarios. Although not identified as an monitoring. Fortunately, there were no long-term Previous recommendations and actions taken by experience symptoms of anaphylaxis; however, these (intended to walk the user through the associated subthemes (see Figure 1). This bulletin issue in this analysis, consider extending this cardiac effects. facilities to support the correct dose and route of devices can be difficult to use if patients or caregivers administration process) in an incorrect language Reports of medication incidents related to describes each of the main themes and selected recommendation to medical office staff.5 epinephrine administration in anaphylaxis are are unfamiliar with them. For example, accidental Other pharmacy processes deemed problematic were • confusion in interpreting ratio expressions for epinephrine were extracted from voluntary reports* subthemes, along with illustrative examples. Wrong-dose and/or wrong-route errors have occurred outlined in Box 1. injection of epinephrine into the thumb of the person dispensing expired epinephrine auto-injectors and epinephrine concentration appearing on labels submitted to three ISMP Canada incident reporting when adults with anaphylaxis have been treated with administering epinephrine has occurred, likely as a failure to enter refills on prescription order entry. databases (Individual Practitioner Reporting, the cardiac resuscitation dose (1 mg IV) rather than Subtheme: Insufficient quantity result of a knowledge gap about device deployment. Conclusion Community Pharmacy Incident Reporting, and the recommended anaphylaxis dose (0.2 to 0.5 mg This type of incident reinforces the need for THEME: Product Flaws Consumer Reporting), and the National System for IM5).6 These errors likely result from the The subtheme of knowledge gaps regarding the practitioners to regularly confirm patients’ and Epinephrine is a critical, life-saving treatment for Incident Reporting† (NSIR) between April 2010 and comprehensive life-saving training required by quantity to be prescribed was apparent in reports in caregivers’ understanding of the proper and safe use Three brands of epinephrine auto-injector—EpiPen, anaphylaxis that can be administered by both Anaphylaxis is an acute, life-threatening, systemic October 2016. emergency practitioners, who subsequently become which too few devices were prescribed for emergency of these devices, both for therapeutic effect and to Twinject, and Allerject—were available in Canada healthcare professionals and the general public. allergic reaction associated with various triggers, more familiar with the cardiac resuscitation than the treatment of anaphylaxis in the community. Current avoid injuries. Practitioners are encouraged to use a during the period from which the data set was Because anaphylaxis can occur anywhere, workers in clinical presentations, and levels of severity.1 The following medication names were used as search anaphylaxis treatment dose of epinephrine in adults. guidelines recommend that each patient be given “teach back” method to confirm patient extracted. The latter 2 brands are no longer marketed. all healthcare sectors are encouraged to review the Epinephrine is the only life-saving drug used to treat terms: “epinephrine”, “adrenalin”, “Epipen”, 2 devices at a time, because up to 30% of anaphylaxis understanding. Common look-alike / sound-alike (LASA) incidents information identified in this analysis and implement a person experiencing anaphylaxis. Recent “Epi-pen”, “Twinject”, “Allerject”, “Anakit”, and In the current multi-incident analysis, dose-related reactions require the administration of more than were reported when prescribers confused Twinject the recommendations in this bulletin to optimize the epidemiological studies indicate that the prevalence “Ana-kit”. Almost 200 incidents were identified in incidents in the community resulted when 1 dose of epinephrine.5 In particular, for children at THEME: Process Problems with Twinrix (hepatitis A and B vaccine). Fortunately, safe and correct use of epinephrine. prescriptions were renewed for the pediatric risk of anaphylaxis, 1 device should be kept at school these errors were caught by community pharmacists auto-injector when, in fact, the child’s current weight and 1 device always with the child, either on their Several reports described patients receiving an during patient counselling. would require that the “adult” device be dispensed. person or with a caregiver. auto-injector device labelled with another person’s

ISMP Canada Safety Bulletin – Volume 17 • Issue 6 • June 29, 2017 4 of 8 the ISMP Canada databases, and 44 were found in the THEME: Knowledge Gaps Subtheme: Wrong dose Because each device is designed to supply only a name. This situation can result when a prescription Incident Example Acknowledgements References NSIR database. Incidents not related to epinephrine single, measured dose when activated, choosing the prepared for a specific patient is returned to stock in A physician wrote a prescription for “Twinrix” with 1. Wood RA, Camargo CA Jr, Lieberman P, Sampson HA, Schwartz LB, Zitt M, et al. Anaphylaxis in America: the prevalence and use in anaphylaxis were excluded, which left 146 Subtheme: Wrong route Incorrect dose incidents with epinephrine have correct one is essential. the pharmacy, because the patient either does not pick 6 refills. The pharmacist clarified with both the ISMP Canada gratefully acknowledges the characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467. incidents in the final analysis. The analysis was occurred in both acute care and community settings. up the prescription or declines to purchase it because patient and the physician that the desired contribution of content by Waleed Alqurashi MD, 2. Tejedor-Alonso MA, Moro Moro M, Múgica-García M. Epidemiology of anaphylaxis: contributions from the last 10 years. J Investig Allergol Clin Immunol. 2015;25(3):163-175. conducted according to the methodology for For anaphylaxis, epinephrine should be administered One potential contributing factor has been use of the of cost. These types of incidents highlight problems medication was Twinject. MSc, FAAP, FRCPC, Assistant Professor, University 3. Anaphylaxis and allergy in the emergency department.Ottawa (ON): Canadian Institute for Health Information; 2015 Sep 10 [cited multi-incident analysis outlined in the Canadian intramuscularly (IM); the intravenous (IV) route of historical ratio expressions (1:1000, 1:10,000) for in 2 community pharmacy processes—the process to of Ottawa Department of Pediatrics and Emergency 2017 Mar 20]. Available from: https://secure.cihi.ca/free_products/Anaphylaxis_Infosheet_en.pdf Incident Analysis Framework.4 administration should be reserved for patients who strength. In 2016, because of an ongoing stream of return a product to stock, and the dispensing process LASA issues were also reported from the hospital Medicine Children’s Hospital of Eastern Ontario 4. Incident Analysis Collaborating Parties. Canadian incident analysis framework. Edmonton (AB): Canadian Patient Safety Institute; have not responded to IM doses and those serious errors related to confusion in understanding for labelling and verification of both the outer setting, where ePHEDrine was mistaken for (CHEO), ON and Ken J Farion MD FRCPC, Medical 2012 [cited 2016 Nov 14]. Incident Analysis Collaborating Parties are Canadian Patient Safety Institute (CPSI), Institute for Safe Quantitative Findings experiencing severe physiologic compromise.5 ratio expressions, the United States Pharmacopoeia packaging and the device inside the box. epinephrine when medication vials were being Director – Quality & Systems Improvement, Medication Practices Canada, Saskatchewan Health, Patients for Patient Safety Canada (a patient-led program of CPSI), Paula Beard, Carolyn E. Hoffman, and Micheline Ste-Marie. Available from: http://www.patientsafetyinstitute.ca/en/toolsResources/Incident Wrong-route administration of epinephrine has been eliminated ratio expressions on single-entity drug re-stocked. Children’s Hospital of Eastern Ontario, Ottawa, ON Analysis/Documents/Canadian%20Incident%20Analysis%20Framework.PDF The majority of the incidents were reported to the previously reported in an ISMP Canada Safety products such as epinephrine.10 Therefore, 1:1000 Incident Example and acknowledges the following individuals for their 5. Lieberman P, Nicklas RA, Randolph C, Oppenheimer J, Bernstein D, Ellis A et al. Anaphylaxis—a practice parameter update 2015. ISMP Canada databases. Of these reports, wrong Bulletin6 and elsewhere in the literature.7,8 In a review epinephrine products are now labelled as 1 mg/mL, An Epi-Pen was dispensed for a child. The expert review of this bulletin: Ann Allergy Asthma Immunol. 2015;115(5):341-384. dose errors (e.g., Epipen Jr. given to a child weighing of more than 600 cases reported to the Pennsylvania while epinephrine 1:10,000 for IV injection is caregiver at school noticed that the device was 6. Alert: wrong route incidents with epinephrine. ISMP Canada Saf Bull 2014 [cited 2017 Feb 2];14(4):1-3. Available from: https://www.ismp-canada.org/download/safetyBulletins/2014/ISMPCSB2014-4_Epinephrine.pdf 30 kg or greater) comprised the most commonly Patient Safety Reporting System, wrong-route errors labelled as 0.1 mg/mL. A second potential factor labelled with someone else’s name, even though the Waleed Alqurashi MD, MSc, FAAP, FRCPC, 7. Campbell RL, Bellolio MF, Knutson BD, Bellamkonda VR, Fedko MG, Nestler DM, et al. Epinephrine in anaphylaxis: higher risk of reported incident type, followed by products being involving IV administration were responsible for contributing to incorrect dosing is the need for a dose Pediatric devices contain an epinephrine dose outer box was labelled correctly. The school Assistant Professor, University of Ottawa Department cardiovascular complications and overdose after administration of intravenous bolus epinephrine compared with intramuscular of anaphylaxis is increasing.2,3 The Canadian Institute prepared for the wrong patient and wrong quantity 25.4% of all epinephrine adverse events and 63.3% of calculation in the pediatric age group. The appropriate for a child weighing between 15 to 30 kg notified the parents, who contacted the pharmacy. of Pediatrics and Emergency Medicine Children’s epinephrine. J Allergy Clin Immunol Pract. 2015;3(1):76-80. for Health Information (CIHI) reported that from dispensed. Over 80% of incidents were caught before the harmful events.8 Several studies have attributed epinephrine dose for anaphylaxis in pediatrics must (i.e., 0.15 mg); the ‘adult’ device delivers 0.3 mg and The pharmacy determined that the device provided Hospital of Eastern Ontario (CHEO), ON; Stephanie 8. An update on the “Epi”demic: events involving EPINEPHrine. Pa Patient Saf Advis. 2009;6(3):102-103. 2006 to 2015, there was a 64% increase in the the error reached the patient. this error to a lack of adequate education of be calculated according to the patient’s weight is recommended for children (and adults) weighing for the child had previously been returned to stock Crampton, RN, BSN, ENC(C), Cornwall Hospital, 9. Cohen MB, Saunders SS, Wise SK, Nassif S, Platt MP. Pitfalls in the use of epinephrine for anaphylaxis: patient and provider 9 11 12 opportunities for improvement. Int Forum Allergy Rhinol. 2017;7(3):276-286. number of individuals for whom an epinephrine healthcare professionals. (0.01 mg/kg, up to a maximum of 0.5 mg); this 30 kg or more. In several of the incidents analyzed, without removal of the old label. Cornwall, ON; Tracy Furst, BSc, BScPharm, 10. Changes in expression of strength: elimination of ratios on single-entity injectable products. ISMP Can Saf Bull 2016 [cited 2017 auto-injector was dispensed, and children were the Of the incidents reported to ISMP Canada databases, calculation step represents a risk for error. verification of the child’s weight at the pharmacy Children's Emergency Department Pharmacist, Feb 12]; 16(2):1-3. Available from: top consumers.3 Because of the increased use of 3.5% of cases resulted in harm to the patient. The Incident Example allowed interception and correction of dosing errors Health Sciences Centre, Winnipeg, MB; Kelly https://www.ismp-canada.org/download/safetyBulletins/2016/ISMPCSB2016-02_ChangesInExpressionStrength.pdf epinephrine, there is a need to better understand the most common type of harm incident resulted from the A consumer reported receiving epinephrine by the Incident Example before they reached the patient. Current guidelines The following manufacturing deficits (which have MacKinnon, BScPharm, Clinical Pharmacist 11. Cheng A, Canadian Pediatric Society (Acute Care Committee). Emergency treatment of anaphylaxis in infants and children [position statement]. Paediatr Child Health 2011 [reaffirmed 2016 Feb 1];16(1):35-40. potential risks and problems associated with use of intravenous administration of epinephrine – either IV route, rather than the recommended IM route, as An infant weighing 6.5 kg was treated with for pediatric use of epinephrine suggest that “giving a since been addressed by the manufacturers), among (Emergency Services), Colchester East Hants Health 12. EpiPen/EpiPen Jr monograph. In: e-CPS. Ottawa (ON): Canadian Pharmacists Association; [cited 2017 May 14]. Available from: this high-alert medication. due to selection of the incorrect route when ordering treatment for a mild allergic reaction while in the epinephrine in the emergency room for a possible dose that is slightly above the ideal dose appears to others, were reported in the analysis: Centre, Truro, NS; Dominick Shelton MD, Medical https://www.e-therapeutics.ca/search [Subscription required to access content]. epinephrine treatment, or wrong-route administration emergency room. She experienced convulsions, anaphylactic reaction. The calculated dose, based be a better option than giving a dose that is below the Director of Quality & Safety, Emergency 13. Risk of mix-ups between ephedrine and epinephrine. ISMP Canada Saf Bull 2007 [cited 2017 Feb 2];7(2):1-3. Available from: A multi-incident analysis was conducted to identify (i.e., IM route ordered, but administered IV). All of angina, tachycardia, a severe headache, and on 0.01 mg/kg, should have been 0.065 mg IM; recommended dose,” given that underdosing may not Subtheme: Erroneous deployment • placement of the wrong bar code on an epinephrine Department, Sunnybrook Health Sciences Centre, https://www.ismp-canada.org/download/safetyBulletins/ISMPCSB2007-02Ephedrine.pdf factors contributing to errors when epinephrine was the wrong-route incidents resulted in harm to the difficulty breathing. As a result, intervention and however, the infant received 0.65 mg IM, 10 times be effective to treat anaphylaxis.5 So for children who product Toronto, ON. used for the treatment of anaphylaxis and to suggest patients. additional monitoring were required. the intended dose. The baby became lethargic, pale, weigh close to 30 kg, practitioners may choose to Accidental or erroneous deployment of the • use of the same Drug Identification Number (DIN; strategies to prevent or minimize potential harm and cyanotic, and experienced cardiac ischemia. prescribe the ‘adult’ device, taking into account auto-injector represents the last knowledge gap used for verification in pharmacy processes) for when epinephrine is used for this indication. Qualitative Findings Clinical areas and teams that need to treat The child required an urgent transfer to a previous reactions and individual risk factors. subtheme. Epinephrine auto-injectors are commonly both English and French Allerject products, which anaphylaxis should receive regular training, including specialized pediatric centre and prolonged carried by patients for self-administration should they led to provision of a voice-enabled device Methodology Analysis revealed 3 main themes, each with multiple holding mock scenarios. Although not identified as an monitoring. Fortunately, there were no long-term Previous recommendations and actions taken by experience symptoms of anaphylaxis; however, these (intended to walk the user through the associated subthemes (see Figure 1). This bulletin issue in this analysis, consider extending this cardiac effects. facilities to support the correct dose and route of devices can be difficult to use if patients or caregivers administration process) in an incorrect language Reports of medication incidents related to describes each of the main themes and selected recommendation to medical office staff.5 epinephrine administration in anaphylaxis are are unfamiliar with them. For example, accidental Other pharmacy processes deemed problematic were • confusion in interpreting ratio expressions for epinephrine were extracted from voluntary reports* subthemes, along with illustrative examples. Wrong-dose and/or wrong-route errors have occurred outlined in Box 1. injection of epinephrine into the thumb of the person dispensing expired epinephrine auto-injectors and epinephrine concentration appearing on labels submitted to three ISMP Canada incident reporting when adults with anaphylaxis have been treated with administering epinephrine has occurred, likely as a failure to enter refills on prescription order entry. databases (Individual Practitioner Reporting, the cardiac resuscitation dose (1 mg IV) rather than Subtheme: Insufficient quantity result of a knowledge gap about device deployment. Conclusion Community Pharmacy Incident Reporting, and the recommended anaphylaxis dose (0.2 to 0.5 mg This type of incident reinforces the need for THEME: Product Flaws Consumer Reporting), and the National System for IM5).6 These errors likely result from the The subtheme of knowledge gaps regarding the practitioners to regularly confirm patients’ and Epinephrine is a critical, life-saving treatment for Incident Reporting† (NSIR) between April 2010 and comprehensive life-saving training required by quantity to be prescribed was apparent in reports in caregivers’ understanding of the proper and safe use Three brands of epinephrine auto-injector—EpiPen, anaphylaxis that can be administered by both Anaphylaxis is an acute, life-threatening, systemic October 2016. emergency practitioners, who subsequently become which too few devices were prescribed for emergency of these devices, both for therapeutic effect and to Twinject, and Allerject—were available in Canada healthcare professionals and the general public. allergic reaction associated with various triggers, more familiar with the cardiac resuscitation than the treatment of anaphylaxis in the community. Current avoid injuries. Practitioners are encouraged to use a during the period from which the data set was Because anaphylaxis can occur anywhere, workers in clinical presentations, and levels of severity.1 The following medication names were used as search anaphylaxis treatment dose of epinephrine in adults. guidelines recommend that each patient be given “teach back” method to confirm patient extracted. The latter 2 brands are no longer marketed. all healthcare sectors are encouraged to review the Epinephrine is the only life-saving drug used to treat terms: “epinephrine”, “adrenalin”, “Epipen”, 2 devices at a time, because up to 30% of anaphylaxis understanding. Common look-alike / sound-alike (LASA) incidents information identified in this analysis and implement a person experiencing anaphylaxis. Recent “Epi-pen”, “Twinject”, “Allerject”, “Anakit”, and In the current multi-incident analysis, dose-related reactions require the administration of more than were reported when prescribers confused Twinject the recommendations in this bulletin to optimize the epidemiological studies indicate that the prevalence “Ana-kit”. Almost 200 incidents were identified in incidents in the community resulted when 1 dose of epinephrine.5 In particular, for children at THEME: Process Problems with Twinrix (hepatitis A and B vaccine). Fortunately, safe and correct use of epinephrine. prescriptions were renewed for the pediatric risk of anaphylaxis, 1 device should be kept at school these errors were caught by community pharmacists auto-injector when, in fact, the child’s current weight and 1 device always with the child, either on their Several reports described patients receiving an during patient counselling. would require that the “adult” device be dispensed. person or with a caregiver. auto-injector device labelled with another person’s

ISMP Canada Safety Bulletin – Volume 17 • Issue 6 • June 29, 2017 5 of 8 the ISMP Canada databases, and 44 were found in the THEME: Knowledge Gaps Subtheme: Wrong dose Because each device is designed to supply only a name. This situation can result when a prescription Incident Example Acknowledgements References NSIR database. Incidents not related to epinephrine single, measured dose when activated, choosing the prepared for a specific patient is returned to stock in A physician wrote a prescription for “Twinrix” with 1. Wood RA, Camargo CA Jr, Lieberman P, Sampson HA, Schwartz LB, Zitt M, et al. Anaphylaxis in America: the prevalence and use in anaphylaxis were excluded, which left 146 Subtheme: Wrong route Incorrect dose incidents with epinephrine have correct one is essential. the pharmacy, because the patient either does not pick 6 refills. The pharmacist clarified with both the ISMP Canada gratefully acknowledges the characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467. incidents in the final analysis. The analysis was occurred in both acute care and community settings. up the prescription or declines to purchase it because patient and the physician that the desired contribution of content by Waleed Alqurashi MD, 2. Tejedor-Alonso MA, Moro Moro M, Múgica-García M. Epidemiology of anaphylaxis: contributions from the last 10 years. J Investig Allergol Clin Immunol. 2015;25(3):163-175. conducted according to the methodology for For anaphylaxis, epinephrine should be administered One potential contributing factor has been use of the of cost. These types of incidents highlight problems medication was Twinject. MSc, FAAP, FRCPC, Assistant Professor, University 3. Anaphylaxis and allergy in the emergency department.Ottawa (ON): Canadian Institute for Health Information; 2015 Sep 10 [cited multi-incident analysis outlined in the Canadian intramuscularly (IM); the intravenous (IV) route of historical ratio expressions (1:1000, 1:10,000) for in 2 community pharmacy processes—the process to of Ottawa Department of Pediatrics and Emergency 2017 Mar 20]. Available from: https://secure.cihi.ca/free_products/Anaphylaxis_Infosheet_en.pdf Incident Analysis Framework.4 administration should be reserved for patients who strength. In 2016, because of an ongoing stream of return a product to stock, and the dispensing process LASA issues were also reported from the hospital Medicine Children’s Hospital of Eastern Ontario 4. Incident Analysis Collaborating Parties. Canadian incident analysis framework. Edmonton (AB): Canadian Patient Safety Institute; have not responded to IM doses and those serious errors related to confusion in understanding for labelling and verification of both the outer setting, where ePHEDrine was mistaken for (CHEO), ON and Ken J Farion MD FRCPC, Medical 2012 [cited 2016 Nov 14]. Incident Analysis Collaborating Parties are Canadian Patient Safety Institute (CPSI), Institute for Safe Quantitative Findings experiencing severe physiologic compromise.5 ratio expressions, the United States Pharmacopoeia packaging and the device inside the box. epinephrine when medication vials were being Director – Quality & Systems Improvement, Medication Practices Canada, Saskatchewan Health, Patients for Patient Safety Canada (a patient-led program of CPSI), Paula Beard, Carolyn E. Hoffman, and Micheline Ste-Marie. Available from: http://www.patientsafetyinstitute.ca/en/toolsResources/Incident Wrong-route administration of epinephrine has been eliminated ratio expressions on single-entity drug re-stocked. Children’s Hospital of Eastern Ontario, Ottawa, ON Analysis/Documents/Canadian%20Incident%20Analysis%20Framework.PDF The majority of the incidents were reported to the previously reported in an ISMP Canada Safety products such as epinephrine.10 Therefore, 1:1000 Incident Example and acknowledges the following individuals for their 5. Lieberman P, Nicklas RA, Randolph C, Oppenheimer J, Bernstein D, Ellis A et al. Anaphylaxis—a practice parameter update 2015. ISMP Canada databases. Of these reports, wrong Bulletin6 and elsewhere in the literature.7,8 In a review epinephrine products are now labelled as 1 mg/mL, An Epi-Pen was dispensed for a child. The expert review of this bulletin: Ann Allergy Asthma Immunol. 2015;115(5):341-384. dose errors (e.g., Epipen Jr. given to a child weighing of more than 600 cases reported to the Pennsylvania while epinephrine 1:10,000 for IV injection is caregiver at school noticed that the device was 6. Alert: wrong route incidents with epinephrine. ISMP Canada Saf Bull 2014 [cited 2017 Feb 2];14(4):1-3. Available from: https://www.ismp-canada.org/download/safetyBulletins/2014/ISMPCSB2014-4_Epinephrine.pdf 30 kg or greater) comprised the most commonly Patient Safety Reporting System, wrong-route errors labelled as 0.1 mg/mL. A second potential factor labelled with someone else’s name, even though the Waleed Alqurashi MD, MSc, FAAP, FRCPC, 7. Campbell RL, Bellolio MF, Knutson BD, Bellamkonda VR, Fedko MG, Nestler DM, et al. Epinephrine in anaphylaxis: higher risk of reported incident type, followed by products being involving IV administration were responsible for contributing to incorrect dosing is the need for a dose Pediatric devices contain an epinephrine dose outer box was labelled correctly. The school Assistant Professor, University of Ottawa Department cardiovascular complications and overdose after administration of intravenous bolus epinephrine compared with intramuscular of anaphylaxis is increasing.2,3 The Canadian Institute prepared for the wrong patient and wrong quantity 25.4% of all epinephrine adverse events and 63.3% of calculation in the pediatric age group. The appropriate for a child weighing between 15 to 30 kg notified the parents, who contacted the pharmacy. of Pediatrics and Emergency Medicine Children’s epinephrine. J Allergy Clin Immunol Pract. 2015;3(1):76-80. for Health Information (CIHI) reported that from dispensed. Over 80% of incidents were caught before the harmful events.8 Several studies have attributed epinephrine dose for anaphylaxis in pediatrics must (i.e., 0.15 mg); the ‘adult’ device delivers 0.3 mg and The pharmacy determined that the device provided Hospital of Eastern Ontario (CHEO), ON; Stephanie 8. An update on the “Epi”demic: events involving EPINEPHrine. Pa Patient Saf Advis. 2009;6(3):102-103. 2006 to 2015, there was a 64% increase in the the error reached the patient. this error to a lack of adequate education of be calculated according to the patient’s weight is recommended for children (and adults) weighing for the child had previously been returned to stock Crampton, RN, BSN, ENC(C), Cornwall Hospital, 9. Cohen MB, Saunders SS, Wise SK, Nassif S, Platt MP. Pitfalls in the use of epinephrine for anaphylaxis: patient and provider 9 11 12 opportunities for improvement. Int Forum Allergy Rhinol. 2017;7(3):276-286. number of individuals for whom an epinephrine healthcare professionals. (0.01 mg/kg, up to a maximum of 0.5 mg); this 30 kg or more. In several of the incidents analyzed, without removal of the old label. Cornwall, ON; Tracy Furst, BSc, BScPharm, 10. Changes in expression of strength: elimination of ratios on single-entity injectable products. ISMP Can Saf Bull 2016 [cited 2017 auto-injector was dispensed, and children were the Of the incidents reported to ISMP Canada databases, calculation step represents a risk for error. verification of the child’s weight at the pharmacy Children's Emergency Department Pharmacist, Feb 12]; 16(2):1-3. Available from: top consumers.3 Because of the increased use of 3.5% of cases resulted in harm to the patient. The Incident Example allowed interception and correction of dosing errors Health Sciences Centre, Winnipeg, MB; Kelly https://www.ismp-canada.org/download/safetyBulletins/2016/ISMPCSB2016-02_ChangesInExpressionStrength.pdf epinephrine, there is a need to better understand the most common type of harm incident resulted from the A consumer reported receiving epinephrine by the Incident Example before they reached the patient. Current guidelines The following manufacturing deficits (which have MacKinnon, BScPharm, Clinical Pharmacist 11. Cheng A, Canadian Pediatric Society (Acute Care Committee). Emergency treatment of anaphylaxis in infants and children [position statement]. Paediatr Child Health 2011 [reaffirmed 2016 Feb 1];16(1):35-40. potential risks and problems associated with use of intravenous administration of epinephrine – either IV route, rather than the recommended IM route, as An infant weighing 6.5 kg was treated with for pediatric use of epinephrine suggest that “giving a since been addressed by the manufacturers), among (Emergency Services), Colchester East Hants Health 12. EpiPen/EpiPen Jr monograph. In: e-CPS. Ottawa (ON): Canadian Pharmacists Association; [cited 2017 May 14]. Available from: this high-alert medication. due to selection of the incorrect route when ordering treatment for a mild allergic reaction while in the epinephrine in the emergency room for a possible dose that is slightly above the ideal dose appears to others, were reported in the analysis: Centre, Truro, NS; Dominick Shelton MD, Medical https://www.e-therapeutics.ca/search [Subscription required to access content]. epinephrine treatment, or wrong-route administration emergency room. She experienced convulsions, anaphylactic reaction. The calculated dose, based be a better option than giving a dose that is below the Director of Quality & Safety, Emergency 13. Risk of mix-ups between ephedrine and epinephrine. ISMP Canada Saf Bull 2007 [cited 2017 Feb 2];7(2):1-3. Available from: A multi-incident analysis was conducted to identify (i.e., IM route ordered, but administered IV). All of angina, tachycardia, a severe headache, and on 0.01 mg/kg, should have been 0.065 mg IM; recommended dose,” given that underdosing may not Subtheme: Erroneous deployment • placement of the wrong bar code on an epinephrine Department, Sunnybrook Health Sciences Centre, https://www.ismp-canada.org/download/safetyBulletins/ISMPCSB2007-02Ephedrine.pdf factors contributing to errors when epinephrine was the wrong-route incidents resulted in harm to the difficulty breathing. As a result, intervention and however, the infant received 0.65 mg IM, 10 times be effective to treat anaphylaxis.5 So for children who product Toronto, ON. used for the treatment of anaphylaxis and to suggest patients. additional monitoring were required. the intended dose. The baby became lethargic, pale, weigh close to 30 kg, practitioners may choose to Accidental or erroneous deployment of the • use of the same Drug Identification Number (DIN; strategies to prevent or minimize potential harm and cyanotic, and experienced cardiac ischemia. prescribe the ‘adult’ device, taking into account auto-injector represents the last knowledge gap used for verification in pharmacy processes) for when epinephrine is used for this indication. Qualitative Findings Clinical areas and teams that need to treat The child required an urgent transfer to a previous reactions and individual risk factors. subtheme. Epinephrine auto-injectors are commonly both English and French Allerject products, which anaphylaxis should receive regular training, including specialized pediatric centre and prolonged carried by patients for self-administration should they led to provision of a voice-enabled device Health Canada Seeking Feedback on Mandatory Reporting of Serious Methodology Analysis revealed 3 main themes, each with multiple holding mock scenarios. Although not identified as an monitoring. Fortunately, there were no long-term Previous recommendations and actions taken by experience symptoms of anaphylaxis; however, these (intended to walk the user through the Adverse Drug Reactions and Medical Device Incidents associated subthemes (see Figure 1). This bulletin issue in this analysis, consider extending this cardiac effects. facilities to support the correct dose and route of devices can be difficult to use if patients or caregivers administration process) in an incorrect language 5 Reports of medication incidents related to describes each of the main themes and selected recommendation to medical office staff. epinephrine administration in anaphylaxis are are unfamiliar with them. For example, accidental Other pharmacy processes deemed problematic were • confusion in interpreting ratio expressions for In late June 2017, Health Canada released the consultation paper “Mandatory Reporting of Serious epinephrine were extracted from voluntary reports* subthemes, along with illustrative examples. Wrong-dose and/or wrong-route errors have occurred outlined in Box 1. injection of epinephrine into the thumb of the person dispensing expired epinephrine auto-injectors and epinephrine concentration appearing on labels Adverse Drug Reactions and Medical Device Incidents by Health Care Institutions” submitted to three ISMP Canada incident reporting when adults with anaphylaxis have been treated with administering epinephrine has occurred, likely as a failure to enter refills on prescription order entry. (https://www.canada.ca/en/health-canada/programs/consultation-reporting-serious-adverse-drug- databases (Individual Practitioner Reporting, the cardiac resuscitation dose (1 mg IV) rather than Subtheme: Insufficient quantity result of a knowledge gap about device deployment. Conclusion reactions-medical-device-incidents.html) in support of the Protecting Canadians from Unsafe Drugs Act Community Pharmacy Incident Reporting, and the recommended anaphylaxis dose (0.2 to 0.5 mg This type of incident reinforces the need for THEME: Product Flaws (Vanessa’s Law). The paper presents proposals for comment, provides alternative options and poses a Consumer Reporting), and the National System for IM5).6 These errors likely result from the The subtheme of knowledge gaps regarding the practitioners to regularly confirm patients’ and Epinephrine is a critical, life-saving treatment for series of questions. Incident Reporting† (NSIR) between April 2010 and comprehensive life-saving training required by quantity to be prescribed was apparent in reports in caregivers’ understanding of the proper and safe use Three brands of epinephrine auto-injector—EpiPen, anaphylaxis that can be administered by both Anaphylaxis is an acute, life-threatening, systemic October 2016. emergency practitioners, who subsequently become which too few devices were prescribed for emergency of these devices, both for therapeutic effect and to Twinject, and Allerject—were available in Canada healthcare professionals and the general public. Health Canada is seeking feedback on the consultation paper. The feedback will provide a foundation for the development of proposed regulations. The deadline for submitting feedback is August 11, 2017. allergic reaction associated with various triggers, more familiar with the cardiac resuscitation than the treatment of anaphylaxis in the community. Current avoid injuries. Practitioners are encouraged to use a during the period from which the data set was Because anaphylaxis can occur anywhere, workers in 1 clinical presentations, and levels of severity. The following medication names were used as search anaphylaxis treatment dose of epinephrine in adults. guidelines recommend that each patient be given “teach back” method to confirm patient extracted. The latter 2 brands are no longer marketed. all healthcare sectors are encouraged to review the Health Canada will be hosting a webinar on Tuesday, July 18, 2017, at 12:30 pm EDT to share information Epinephrine is the only life-saving drug used to treat terms: “epinephrine”, “adrenalin”, “Epipen”, 2 devices at a time, because up to 30% of anaphylaxis understanding. Common look-alike / sound-alike (LASA) incidents information identified in this analysis and implement on the proposals within the consultation paper. Questions may be sent in advance to be answered by a person experiencing anaphylaxis. Recent “Epi-pen”, “Twinject”, “Allerject”, “Anakit”, and In the current multi-incident analysis, dose-related reactions require the administration of more than were reported when prescribers confused Twinject the recommendations in this bulletin to optimize the Health Canada during the webinar. Those interested in participating in the webinar should register by epidemiological studies indicate that the prevalence “Ana-kit”. Almost 200 incidents were identified in incidents in the community resulted when 1 dose of epinephrine.5 In particular, for children at THEME: Process Problems with Twinrix (hepatitis A and B vaccine). Fortunately, safe and correct use of epinephrine. Wednesday, July 12, 2017, by sending their name and email address to: prescriptions were renewed for the pediatric risk of anaphylaxis, 1 device should be kept at school these errors were caught by community pharmacists [email protected] auto-injector when, in fact, the child’s current weight and 1 device always with the child, either on their Several reports described patients receiving an during patient counselling. would require that the “adult” device be dispensed. person or with a caregiver. auto-injector device labelled with another person’s

ISMP Canada Safety Bulletin – Volume 17 • Issue 6 • June 29, 2017 6 of 8 This segment of the bulletin describes a recent SafeMedicationUse.ca publication from ISMP Canada’s Consumer Program.

June 2017 Newsletter: Losing Medications Can Spoil Your Vacation

SafeMedicationUse.ca received a report from a consumer who lost his medications while on vacation. The newsletter provided recommendations for consumers on how to prevent the loss of medications while travelling, including the best ways to store medications during transit. Advice on dealing with lost or forgotten medications while away from home was also shared. Tips for Practitioners: • Give each of your patients a medication list, and help them to update it regularly. Updating this list is especially important before vacations and any other extended travel. • Explain to your patients the purpose of each medication and how it should be taken. This information will be helpful if new prescriptions are needed in another country. For more information, read the full newsletter: https://safemedicationuse.ca/newsletter/newsletter_LosingMeds.html

Updated Labelling and Packaging Guide Will Make It Easier for Canadians to Use Health Products Safely

A newly revised guide released by Health Canada is expected to improve the safe use of nonprescription and natural health products by making labels easier for consumers to read and understand. In particular, the guide aims to ensure the prominence of critical information on product labels.

The updated guide incorporates requirements from Canada’s Plain Language Labelling Regulations, such as the Drug Facts table for nonprescription drugs. Regulated parties must be in compliance as of June 30, 2021.

For more information, the revised Good Label and Package Practices Guide for Non-prescription Drugs and Natural Health Products is available at: https://www.canada.ca/en/health-canada/services/ drugs-health-products/reports-publications/medeffect-canada/good-label-package-practices-guide-non- prescription-drugs-natural-health-products.html

ISMP Canada Safety Bulletin – Volume 17 • Issue 6 • June 29, 2017 7 of 8 Report Medication Incidents (Including near misses) The Canadian Medication Incident Reporting and Prevention Online: www.ismp-canada.org/err_index.htm System (CMIRPS) is a collaborative pan-Canadian program of Phone: 1-866-544-7672 Health Canada, the Canadian Institute for Health Information (CIHI), the Institute for Safe Medication Practices Canada ISMP Canada strives to ensure confidentiality and security of information received, and respects the wishes (ISMP Canada) and the Canadian Patient Safety Institute of the reporter as to the level of detail to be included in (CPSI). The goal of CMIRPS is to reduce and prevent harmful publications. Medication Safety bulletins contribute to medication incidents in Canada. Global Patient Safety Alerts. Stay Informed To receive ISMP Canada Safety Bulletins and Newsletters visit: The Healthcare Insurance Reciprocal of Canada (HIROC) www.ismp-canada.org/stayinformed/ provides support for the bulletin and is a member owned expert provider of professional and general liability coverage This bulletin shares information about safe medication and risk management support. practices, is noncommercial, and is therefore exempt from Canadian anti-spam legislation.

Contact Us Email: [email protected] The Institute for Safe Medication Practices Canada (ISMP Phone: 1-866-544-7672 Canada) is an independent national not-for-profit ©2017 Institute for Safe Medication Practices Canada. organization committed to the advancement of medication safety in all healthcare settings. ISMP Canada's mandate includes analyzing medication incidents, making recommendations for the prevention of harmful medication incidents, and facilitating quality improvement initiatives.

ISMP Canada Safety Bulletin – Volume 17 • Issue 6 • June 29, 2017 8 of 8